Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Rd, Nanjing, 210029, China.
Ann Hematol. 2014 Mar;93(3):425-35. doi: 10.1007/s00277-013-1883-1. Epub 2013 Aug 25.
Bcl-2-associated athanogene 3 (BAG3), a member of BAG family, is shown to sustain cell survival and underlie resistance to chemotherapy in human neoplastic cells. We aimed to determine the exact role and underlying mechanisms of BAG3 in human chronic lymphocytic leukemia (CLL). One hundred human CLL samples and 20 normal B-cell samples from healthy controls were collected. We measured the BAG3 expression in these cells and explored its relationship with known prognostic factors for CLL. The roles of BAG3 in cell apoptosis and migration were evaluated by small interfering RNA-mediated knockdown of BAG3 in primary CLL cells. We showed that BAG3 expression level was increased in CLL cells compared with normal B cells. Moreover, BAG3 expression was particularly upregulated in CD38 positive, unmutated immunoglobulin heavy-chain patients and those with lymphadenopathy and/or splenomegaly. Importantly, patients with increased BAG3 expression level have poor overall survival in subgroups with positive ZAP-70 or those without any "p53 abnormality". In addition, knocking down of BAG3 expression resulted in increased apoptotic ratio and decreased migration in primary CLL cells. Our data indicate that BAG3 is a marker of poor prognostic in specific subgroups of CLL patients and may be a potential therapeutic target for this disease.
Bcl-2 相关抗凋亡基因 3（BAG3）是 BAG 家族的一员，其可维持细胞存活并为人类肿瘤细胞对化疗产生耐药性提供基础。我们旨在确定 BAG3 在人类慢性淋巴细胞白血病（CLL）中的确切作用和潜在机制。收集了 100 例人类 CLL 样本和 20 例来自健康对照者的正常 B 细胞样本。我们测量了这些细胞中的 BAG3 表达情况，并探讨了其与 CLL 已知预后因素的关系。通过在原代 CLL 细胞中用小干扰 RNA 介导的 BAG3 敲低来评估 BAG3 在细胞凋亡和迁移中的作用。我们发现 CLL 细胞中的 BAG3 表达水平高于正常 B 细胞。此外，在 CD38 阳性、未突变免疫球蛋白重链患者以及有淋巴结病和/或脾肿大的患者中，BAG3 表达上调尤为明显。重要的是，在 ZAP-70 阳性亚组或无任何“p53 异常”的亚组中，BAG3 表达水平增加的患者总体生存率较差。此外，敲低 BAG3 表达可导致原代 CLL 细胞凋亡比例增加和迁移减少。我们的数据表明，BAG3 是特定 CLL 患者亚组中预后不良的标志物，可能是该疾病的潜在治疗靶点。
